Mapping the distribution of conformational information throughout a protein sequence.

Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Sáenz Peña 180, (1876) Bernal, Buenos Aires, Argentina.
Journal of Molecular Biology (Impact Factor: 3.96). 05/2006; 358(1):280-8. DOI: 10.1016/j.jmb.2006.01.095
Source: PubMed

ABSTRACT The three-dimensional structure of protein is encoded in the sequence, but many amino acid residues carry no essential conformational information, and the identity of those that are structure-determining is elusive. By circular permutation and terminal deletion, we produced and purified 25 Bacillus licheniformis beta-lactamase (ESBL) variants that lack 5-21 contiguous residues each, and collectively have 82% of the sequence and 92% of the non-local atom-atom contacts eliminated. Circular dichroism and size-exclusion chromatography showed that most of the variants form conformationally heterogeneous mixtures, but by measuring catalytic constants, we found that all populate, to a greater or lesser extent, conformations with the essential features of the native fold. This suggests that no segment of the ESBL sequence is essential to the structure as a whole, which is congruent with the notion that local information and modular organization can impart most of the tertiary fold specificity and cooperativity.

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